We will identify and exploit the physiological targets of unique naturally-occurring antibiotics which exhibit specific activity against the causative agent of tuberculosis and related pathogens. Preliminary results have shown tat one or more substances isolated directly from a unique natural product source, selectively inhibit pathogenic mycobacteria in culture. In Phase I of the project, we will determine whether the natural product(s) are truly distinct from previously characterized antimycobacterial drugs. Results consistent with novel activity would justify additional research aimed at developing new antibiotics effective against tuberculosis, a vast and increasingly intractable health problem in the general population, and against closely-related mycobacteria responsible for some of the most common opportunistic infections of AIDS patients.